Ultrastructural analysis of hippocampal pyramidal neurons from apolipoprotein E-deficient mice treated with a cathepsin inhibitor

Cultured hippocampal slices prepared from apolipoprotein E (apoE)-deficient mice were exposed to an inhibitor of cathepsins B and L and then processed for an ultrastructural analysis of neuronal features for pyramidal cell bodies. Electron microscopy showed that the nuclei of pyramidal cells from treated hippocampal slices were more eccentrically located than those from untreated slices. In addition, increased numbers of vesicles were associated with the Golgi complex while microtubules were less frequent in the proximal dendrites. Consistent with previous studies in rats, treated apoE-deficient slices had increased numbers of lysosomes and multivesicular bodies. Finally, there were reductions in the number of synapses around the cell body, a finding similar to that found in the brains from Alzheimer's disease patients. These results provide ultrastructural data indicating that partial lysosomal dysfunction in apoE-deficient brains rapidly induces characteristic features of the aged human brain.     

Phage types and genotypes of shiga toxin-producing Escherichia coli O157:H7 isolates from humans and animals in spain: identification and characterization of two predominating phage types (PT2 and PT8)

Phage typing and DNA macrorestriction fragment analysis by pulsed-field electrophoresis (PFGE) were used for the epidemiological subtyping of a collection of Shiga toxin-producing Escherichia coli (STEC) O157:H7 strains isolated in Spain between 1980 and 1999. Phage typing distinguished a total of 18 phage types among 171 strains isolated from different sources (67 humans, 82 bovines, 12 ovines, and 10 beef products). However, five phage types, phage type 2 (PT2; 42 strains), PT8 (33 strains), PT14 (14 strains), PT21/28 (11 strains), and PT54 (16 strains), accounted for 68% of the study isolates. PT2 and PT8 were the most frequently found among strains from both humans (51%) and bovines (46%). Interestingly, we detected a significant association between PT2 and PT14 and the presence of acute pathologies. A group of 108 of the 171 strains were analyzed by PFGE, and 53 distinct XbaI macrorestriction patterns were identified, with 38 strains exhibiting unique PFGE patterns. In contrast, phage typing identified 15 different phage types. A total of 66 phage type-PFGE subtype combinations were identified among the 108 strains. PFGE subtyping differentiated between unrelated strains that exhibited the same phage type. The most common phage type-PFGE pattern combinations were PT2-PFGE type 1 (1 human and 11 bovine strains), PT8-PFGE type 8 (2 human, 6 bovine, and 1 beef product strains), PT2-PFGE subtype 4A (1 human, 3 bovine, and 1 beef product strains). Nine (29%) of 31 human strains showed phage type-PFGE pattern combinations that were detected among the bovine strains included in this study, and 26 (38%) of 68 bovine strains produced phage type-PFGE pattern combinations observed among human strains included in this study, confirming that cattle are a major reservoir of strains pathogenic for humans. PT2 and PT8 strains formed two groups which differed from each other in their motilities, stx genotypes, PFGE patterns, and the severity of the illnesses that they caused.     

Antimicrobial resistance of Shiga toxin (verotoxin)-producing Escherichia coli O157:H7 and non-O157 strains isolated from humans, cattle, sheep and food in Spain

A total of 722 Shiga toxin-producing Escherichia coli (STEC) isolates recovered from humans, cattle, ovines and food during the period from 1992 to 1999 in Spain were examined to determine antimicrobial resistance profiles and their association with serotypes, phage types and virulence genes. Fifty-eight (41%) out of 141 STEC O157:H7 strains and 240 (41%) out of 581 non-O157 STEC strains showed resistance to at least one of the 26 antimicrobial agents tested. STEC O157:H7 showed a higher percentage of resistant strains recovered from bovine (53%) and beef meat (57%) than from human (23%) and ovine (20%) sources, whereas the highest prevalence of antimicrobial resistance in non-O157 STEC was found among isolates recovered from beef meat (55%) and human patients (47%). Sulfisoxazole (36%) had the most common antimicrobial resistance, followed by tetracycline (32%), streptomycin (29%), ampicillin (10%), trimethoprim (8%), cotrimoxazole (8%), chloramphenicol (7%), kanamycin (7%), piperacillin (6%), and neomycin (5%). The multiple resistance pattern most often observed was that of streptomycin, sulfisoxazole, and tetracycline. Ten (7%) STEC O157:H7 and 71 (12%) non-O157 strains were resistant to five or more antimicrobial agents. Most strains showing resistance to five or more antimicrobial agents belonged to serotypes O4:H4 (4 strains), O8:H21 (3 strains), O20:H19 (6 strains), O26:H11 (8 strains eae-beta1), O111:H- (3 strains eae-gamma2), O118:H- (2 strains eae-beta1), O118:H16 (5 strains eae-beta1), O128:H- (2 strains), O145:H8 or O145:H- (2 strains eae-gamma1), O157:H7 (10 strains eae-gamma1), O171:H25 (3 strains), O177:H11 (5 strains eae-beta1), ONT:H- (3 strains/1 eae-beta1) and ONT:H21 (2 strains). Interestingly, most of these serotypes, i.e., those indicated in bold) were found among human STEC strains isolated from patients with hemolytic uremic-syndrome (HUS) reported in previous studies. We also detected, among non-O157 strains, an association between a higher level of multiple resistance to antibiotics and the presence of the virulence genes eae and stx(1). Moreover, STEC O157:H7, showed an association between certain phage types, PT21/28 (90%), PT23 (75%), PT34 (75%), and PT2 (54%), with a higher number of resistant strains. We conclude that the high prevalence of antimicrobial resistance detected in our study is a source of concern, and cautious use of antibiotics in animals is highly recommended.     

Renosplenic Shunting in the Nutcracker Phenomenon: A Discussion and Paradigm Shift in Options? A Novel Approach to Treating Nutcracker Syndrome

The nutcracker syndrome is a rare clinical manifestation of symptoms caused by the compression of the left renal vein by an overriding superior mesenteric artery, an anatomical variant otherwise known as the nutcracker phenomenon. Usually present in women and children, when symptomatic, it commonly presents with hematuria, proteinuria, and chronic pelvic pain. Effective modalities of treatment apart from conservative management, include both invasive surgical procedures such as renal vein transposition and autotransplantation of the kidney and more popular recently, the less invasive endovascular stenting. Both options, however, are not without complications, such as, retroperitoneal hematomas or stent migration, thrombosis and restenosis. We now present a case of spontaneous renosplenic shunting in a 68-year-old lady of Chinese descent with the nutcracker syndrome—the first of such cases to be ever reported in a patient with no preexisting predilection for chronic liver disease and portosystemic shunting. Despite having significant pelvic venous congestion as evident on computed tomography scans, she remained asymptomatic. This may present a novel paradigm shift for the treatment of the nutcracker syndrome —surgical creation of a renosplenic bypass instead of current modalities, an alternative solution which can be performed laparoscopically and is without problems related to stent use. The creation of laparoscopic splenorenal bypass has been reported once thus far in Cleveland Ohio by Chung and Gill with good symptomatic improvement but no further studies since to validate its long-term effectiveness.     

Dialectical Behavior Therapy in the Treatment of Borderline Personality Disorder and Eating Disorders Comorbidity: A Pilot Study in a Naturalistic Setting

Dialectical behavior therapy (DBT) has been shown to be successful in the treatment of borderline personality disorder and eating disorders separately. The present study compares Standard Dialectical Behavior Therapy with a Treatment as Usual Cognitive Behavior Therapy (TAU CBT) for the treatment of borderline personality disorder and eating disorders comorbid features. A total of 118 women diagnosed with borderline personality disorders and eating disorders were assigned to one of two treatment groups in a naturalistic setting (DBT?=?71; TAU CBT?=?47). DBT showed a greater decrease in dysfunctional behaviors used to regulate emotions and related to borderline personality disorder (i.e. substance abuse, impulsive money spending, unprotected sex, etc.), non-suicidal self-injuries, and depressive symptoms, as well as an increase in cognitive reappraisal and global functioning. DBT and TAU CBT showed similar improvements in suicide attempts, dysfunctional eating behaviors (i.e. binge eating, purgative behaviors, and restriction), hospitalizations, negative and positive affect, and expressive suppression. Results of this study support the utility and effectiveness of standard DBT for comorbid borderline personality disorder and eating disorders in naturalistic settings. Replications of this study and randomized controlled trials are needed.     

Dialectical Behavior Therapy in the Treatment of Comorbid Borderline Personality Disorder and Eating Disorder in a Naturalistic Setting: A Six-Year Follow-up Study

Cognitive Therapy and Research - Dialectical Behavior Therapy (DBT) has shown evidence of its effectiveness in the treatment of borderline personality disorder (BPD) and eating disorders (EDs)...     

Confirmatory factor analysis and psychometric properties of the Emotion Regulation Questionnaire in participants with personality disorders

Emotional dysregulation is a key symptom in participants with personality disorders. The Emotional Regulation Questionnaire (ERQ) has been studied with nonclinical samples; however, it is necessary to confirm the factorial structure of the ERQ in participants with personality disorders. The aims of the present study were to confirm the factorial structure of the Spanish version of the ERQ and analyse its psychometric properties as well as the association between the ERQ and the Borderline Symptoms List (BSL-23) and the Difficulties in Emotion Regulation Scale (DERS). The overall sample was composed of 250 patients with personality disorders, of whom 195 met the criteria for borderline personality disorder. Confirmatory factor analysis was conducted. The two-factor model showed an acceptable fit, similar to the original structure, in the participants with personality disorders and with borderline personality disorder. Cognitive reappraisal was negatively correlated with the DERS and BSL-23, and expressive suppression was positively correlated with the BSL-23. The ERQ is a reliable and valid instrument to evaluate emotional dysregulation in participants with personality disorders and participants with borderline personality disorder.     

Methicillin-resistant Staphylococcus aureus meningitis in adults: a multicenter study of 86 cases

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is an uncommon disease, and little is known about its epidemiology, clinical features, therapy, and outcome. We performed a multicenter retrospective study of MRSA meningitis in adults. Eighty-six adult patients were included and the following data were obtained: underlying diseases, clinical presentation, analytical and microbiologic data, response to therapy, and outcome.There were 56 men (65%) and the mean age was 51.5 years; 54 of them (63%) had severe comorbidities. There were 78 cases of postoperative meningitis and 8 of spontaneous meningitis. The infection was nosocomial in 93% (80/86) of the cases. Among the 78 patients with postoperative meningitis, the most common predisposing conditions were cerebrospinal fluid (CSF) devices (74%), neurosurgery (45%), CSF leakage (17%), and head trauma (12%). Most patients had fever (89%), altered mental status (68%), headache (40%), and meningeal signs (29%). The most common CSF findings were pleocytosis (90%), elevated protein level (77%), and hypoglycorrhachia (30%). CSF Gram stain and blood cultures were positive in 49% (32/65) and 36% (16/45) of cases, respectively. An associated MRSA infection and polymicrobial meningitis appeared in 33% (28/86) and 23% (20/86) of cases, respectively. Antimicrobial therapy was given to 84 patients. Most of them received vancomycin (92%) either as monotherapy (64%) or in combination with other antibiotics (28%), for a median of 18 days. Overall 30-day mortality was 31% (27/86). Multivariate study identified 2 independent factors associated with mortality: spontaneous meningitis (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-195.4; p = 0.007), and coma (OR, 9.7; 95% CI, 2.2-42.3; p = 0.002).In conclusion, MRSA is a relatively uncommon but serious disease. Although most cases are nosocomial infections appearing in neurosurgical patients, spontaneous meningitis may present as a community-onset infection in patients with severe comorbidities requiring frequent contact with the health care system. Most patients have a favorable response to vancomycin, but the beneficial effect of combined and intraventricular therapy, or alternative drugs, remains unclear. MRSA meningitis is associated with a high mortality, and the presence of spontaneous infection and coma are the most important prognostic factors.